Benzodiazepine dependence: Avoidance and withdrawal.

Benzodiazepine dependence remains a shadowy concept. Dependence undoubtedly exists but also acts as an umbrella concept for the underlying chronic morbidity associated with neurosis. Treatment should be directed at early detection and vigorous treatment of anxiety disorders; and an acceptance that long-term treatment may be necessary. Once benzodiazepine dependence is established, each patient requires careful evaluation to establish their unique problem and to institute individual treatment plans. Strategies for benzodiazepine withdrawal are documented but each has its own problems and success can only be achieved if underlying problems are dealt with as well as simply providing tranquilliser withdrawal.

The role of coping strategies in protecting individuals against long-term tranquillizer use.

This research examined the influences of social circumstances, coping and level and length of drug intake on dependence and withdrawal from benzodiazepine use. A sample of long-term benzodiazepine users were followed up over a period of six months. At first interview the participants' drug intake and anxiety and depression levels were established and the Life Events and Difficulties Schedule (LEDS) was administered. At follow up these measures were repeated and individuals' coping strategies for dealing with dependence were also assessed. By the time of the follow-up interview slightly more than half of the participants (57 per cent) had either withdrawn completely from benzodiazepine medication or had reduced their daily dose. Analyses showed that reduction was unrelated to factors associated with the drugs themselves, to the severity of life-events and difficulties, to lessening of difficulties or to the occurrence of positive life-events. Significant associations, however, were found between participants' coping responses in relation to long-term benzodiazepine use and the individuals' reduction or cessation of benzodiazepine use in the six month study period. The study showed that in the absence of positive life-events and in spite of ongoing difficulties actively confronting the problems of benzodiazepine use can have a positive effect on outcome. The findings suggest that interventions which encourage cognitive, behavioural and affective aspects of coping are those which would appear to be most likely to succeed.

A controlled trial of dothiepin and placebo in treating benzodiazepine withdrawal symptoms.

BACKGROUND: The possibility that treatment with tricyclic antidepressants, in the form of dothiepin, might attenuate benzodiazepine withdrawal symptoms was investigated in a double-blind trial. METHOD: Eighty-seven non-depressed psychiatric out-patients with putative normal dose benzodiazepine dependence had their benzodiazepines reduced in stepwise amounts of 20% of the original dose for eight weeks. The patients were randomised to receive dothiepin (with dosage increasing to 150 mg/day) or placebo as an aid to withdrawal before benzodiazepine reduction and these drugs were taken for four further weeks before being stopped. RESULTS: Fewer patients entered and completed the study than expected and a Type II error was possible in the results. Although there was some evidence of withdrawal symptoms being less marked in those patients allocated to dothiepin this was independent of any antidepressant effect as depression scores were lower in the placebo group in the early phase of withdrawal (P < 0.01). Of those completing the study, greater satisfaction (P = 0.03) was recorded by those who had received dothiepin; no other differences reached statistical significance. CONCLUSIONS: Dothiepin (and by implication other tricyclic antidepressants) might have some value in reducing benzodiazepine withdrawal symptoms but does not aid drug withdrawal.

Comparison of long-term benzodiazepine users in three settings.

BACKGROUND: Most studies of chronic benzodiazepine users consider selected populations which may be unrepresentative. This study was undertaken to examine possible differences between groups. METHOD: Subjects chosen were benzodiazepine users in general practice, a hospital clinic, and attending TRANX trials. Descriptive data were collected on characteristics and outcome. RESULTS: TRANX trial patients had the best outcome (P = 0.027). Hospital cases used high doses of anxiolytic benzodiazepines; concomitant mental disorder, including schizophrenia, was common. General practice cases were older and mainly used hypnotics (P < 0.05). CONCLUSIONS: Because groups of benzodiazepine users are different, there cannot be one single management approach. Cases require individual medical assessment.

Guidelines for treating depressive illness with antidepressants: A statement from the British Association for Psychopharmacology.

Depression is a common illness which affects some 3% of the population per year. At least 25% of those with marked depression do not consult their general practitioner and in half of those who do the illness is not detected. Depression is easy to recognize when four or five of the core symptoms have been present for 2 weeks which often coincides with some occupational and social impairment. The core symptoms are depressed mood, loss of interest or pleasure, loss of energy or fatigue, concentration difficulties, appetite disturbance, sleep disturbance, agitation or retardation, worthlessness or self blame and suicidal thoughts. A diagnosis of depression is made when five of these core symptoms, one of which should be depressed mood or loss of interest or pleasure, have been present for 2 weeks. Four core symptoms are probably sufficient. Response to antidepressants is good in those with more than mild symptoms. When there are only few or very mild depressive symptoms evidence of response to antidepressants is more uncertain. Antidepressants are effective, they are not addictive and do not lose efficacy with prolonged use. The newer antidepressants have fewer side effects than the older tricyclics, they are better tolerated and lead to less withdrawals from treatment. They are less cardiotoxic and are safer in overdose. Antidepressants should be used at full therapeutic doses. Treatment failure is often due to too low a dose being used in general practice. It may be difficult to reach the right dose with the older tricyclics because of side effects. To consolidate response, treatment should be continued for at least 4 months after the patient is apparently well. Stopping the treatment before this is ill-advised as the partially treated depression frequently returns. Most depression is recurrent. Long-term antidepressant treatment is effective in reducing the risk of new episodes of depression and should be continued to keep the patient well.

Inadequate treatment response to des-enkephalin-gamma-endorphin compared with thioridazine and placebo in schizophrenia.

The possibility of an involvement of peptidergic systems in schizophrenia has been under investigation for a number of years. Studies of the efficacy of des-tyr-gamma-endorphin were equivocal; more recent studies with des-enkephalin-gamma-endorphin have reported some activity but the peptide has only been investigated as an adjunct to neuroleptic medication, apart from one very small active reference comparator study. In the multicentre study reported here, 96 patients suffering from schizophrenia (DSM-III with a current exacerbation if chronic) were allocated randomly to double-blind treatment with either des-enkephalin-gamma-endorphin (DE-gamma-E) (Org 5878) 10 mg given as a once daily intramuscular injection for 4 weeks, thioridazine 400 mg orally in 2 divided doses or placebo using a double-dummy technique to preserve blindness. There was a significant advantage for thioridazine compared with placebo registered on all measures at weeks 3 and 4. There was no difference between DE-gamma-E and placebo. There was a significant difference between thioridazine and DE-gamma-E at weeks 3 and 4 registered on the MSS and at week 3 registered on the BPRS. The lack of efficacy of DE-gamma-E suggests that the theories that the endorphins have an important role in schizophrenia have to be revised. The need for well designed placebo controlled studies for assessing efficacy in schizophrenia is emphasized.

Self-help and benzodiazepine withdrawal.

Despite an increased understanding of the potential dangers of benzodiazepines among doctors and patients, and a decline in anxiolytic prescribing, motivating and supporting current benzodiazepine users through withdrawal can be difficult and time consuming for medical services. Self-help organisations offer another approach. This is a study of one such organisation, TRANX (UK), which examined the characteristics of its members and their outcome. The results suggest that this organisation did provide effective counselling and support for its members, and implies that self-help is a realistic alternative or adjunct to orthodox health care for those wishing to withdraw from benzodiazepines.

An open study of remoxipride in the long-term treatment of schizophrenia-.

An open non-comparative multicentre study was carried out to evaluate the safety and tolerability of remoxipride over a treatment period of 12 months. The efficacy of the drug in controlling psychotic symptoms was also monitored. Eighty-five men and women aged 18-69 who met the Research Diagnostic Criteria for schizophrenia were entered into the study and after withdrawal of previous antipsychotic medication, treated orally with remoxipride 75-300 mg b.i.d. The treatment was well tolerated and most of the adverse symptoms reported were reduced in incidence at the last rating compared to baseline. Sleep problems (insomnia and increased sleep) and increased thirst showed an increase in incidence during treatment. The incidence of extrapyramidal side effects was low and less than at baseline; there was no evidence that remoxipride produced an increase in abnormal involuntary movements, the median weight of the group did not alter and remoxipride produced no significant effect on cardiovascular, clinical chemistry and haematology variables. It appeared effective in controlling psychotic symptoms and produced some improvement on over one third of the patients despite the fact that the majority of patients entered were not in a productive phase of their illness. The results indicate that remoxipride will be well tolerated and effective when given for the maintenance treatment of schizophrenia.

The treatment of tranquilizer dependence by propranolol.

Forty four subjects were treated for benzodiazepine dependence. The withdrawal programme lasted for 10 weeks and included regular group support sessions. Patients were also treated with either propranolol, placebo or "no pill" under double blind conditions. Twenty three patients complied with the full treatment regimen and completed the trial. The outcome of treatment was moderately successful, with 8 out of the 23 patients stopping their tranquilizers and a further 11 achieving a reduction of 50% or more of their original benzodiazepine dose. Tranquilizer dependence is a difficult condition to treat, but preliminary results suggest that propranolol is helpful in reducing the symptoms of benzodiazepine withdrawal.

Benzodiazepine dependent patients and their psychological treatment.

1. 91 patients were referred to a tranquilizer withdrawal clinic. 44 of these entered a withdrawal programme. The characteristics of the patients are described. 2. 72% of patients accepted for benzodiazepine withdrawal had a history of previous psychiatric contact. They also had significantly higher scores on S.T.A.I. than control groups of non-psychotic psychiatric out-patients indicating a considerable psychiatric morbidity prior to withdrawal. 3. 12 patients were treated with psychological group therapy using anxiety management techniques. The outcome of this pilot study showed that 50% of subjects were able to discontinue their benzodiazepines despite previous failures. 4. Patients found learning to cope with symptoms, sharing problems with others and learning to change thoughts the most useful components of the anxiety management package during withdrawal.